Sheridan, John

John Sheridan, Ph.D., Professor,
The George C. Paffenbarger Alumni-Endowed Chair in Dental Research
Section of Oral Biology
College of Dentistry

Research Interests
Professor Sheridan’s research is devoted to understanding mind body interactions as they relate to host defense against infectious disease.  His interests include neuroendocrine regulation of gene expression in wound healing, inflammatory and immune responses, stress-induced susceptibility to infectious disease, viral pathogenesis and host immunity.  Professor Sheridan has published more than 100 journal articles and chapters.  His current studies examine stress-induced cellular and molecular mechanisms that affect immunity and resistance to infectious disease.  To date, these studies have demonstrated the importance of the hypothalamic-pituitary-adrenal axis in viral pathogenesis, resistance to infectious disease, response to vaccines and wound healing.  This research has been supported by the NIH (NIDCR, NIMH, NIA, NHBLI and NIAID), the World Health Organization, and the John D. and Catherine T. MacArthur Foundation.

There are three major research areas of interest in Dr. Sheridan's laboratory:  the first is viral immunology, the second is neuroendocrine immunology and behavioral medicine, and the third is tissue repair/wound healing. 

Studies in the laboratory have been critical in defining the cellular and molecular mechanisms by which altered behavioral states, such as stress, affect the immune response.  These studies have demonstrated the importance of the hypothalamic-pituitary-adrenal axis on viral disease, the effectiveness of vaccination, and wound healing.  His laboratory continues to be at the forefront of developing animal models for common viral pathogens that have widespread clinical significance, including an influenza model that affects pulmonary function, and a herpes simplex virus model that leads to debilitating neural involvement. 

Dr. Sheridan's research in non-infectious models has been directed at elucidating how stress and neuroendocrine variables impact inflammation, asthma and wound healing.  This intricate process is vital to virtually every aspect of medicine and appears highly susceptible to modulation by social, behavioral, and psychological variables. 

Recently, using a model of social disruption stress, his lab has shown that subordinate animals, but not dominant animals, develop ‘glucocorticoid resistance.’ CD11b+ splenocytes from socially-stressed, subordinate animals become insensitive to regulation by glucocorticoid hormones.  During social stress, the inflammatory response is involved in the repair of cutaneous wounds that often occur during the aggressive interactions. The development of glucocorticoid resistance specifically in spleen cells may suggest that this process is important for the process of healing of wounds.  High levels of corticosterone during social stress could inhibit inflammation and in turn lead to impaired healing or infection of bite-wounds. Therefore, glucocorticoid resistance might occur during social stress to augment the development of the inflammatory responses necessary for wound repair.

Selected Publications
Bailey MT, Engler H, Sheridan JF. Stress induces the translocation of cutaneous and gastrointestinal microflora to secondary lymphoid organs of C57BL/6 mice. J Neuroimmunol. 2006, 171:29-37.

Avitsur R, Hunzeker J, Sheridan JF. Role of early stress in the individual differences in host response to viral infection. Brain Behav Immun. 2005 Nov 10; [Epub ahead of print]

Rosenkranz MA, Busse WW, Johnstone T, Swenson CA, Crisafi GM, Jackson MM, Bosch JA, Sheridan JF, Davidson RJ. Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation. Proc Natl Acad Sci 2005, 102:13319-24.

Avitsur R, Kavelaars A, Heijnen C, Sheridan JF. Social stress and the regulation of tumor necrosis factor-alpha secretion. Brain Behav Immun. 2005 Jul;19(4):311-7. [Epub 2004 Nov 21]

Engler H, Engler A, Bailey MT, Sheridan JF. Tissue-specific alterations in the glucocorticoid sensitivity of immune cells following repeated social defeat in mice. J Neuroimmunol. 2005 Jun;163(1-2):110-9. [Epub 2005 Apr 20]

Engler A, Roy S, Sen CK, Padgett DA, Sheridan JF. Restraint stress alters lung gene expression in an experimental influenza A viral infection. J Neuroimmunol. 2005 May;162(1-2):103-11.

Tseng RJ, Padgett DA, Dhabhar FS, Engler H, Sheridan JF. Stress-induced modulation of NK activity during influenza viral infection: role of glucocorticoids and opioids. Brain Behav Immun. 2005 Mar;19(2):153-64.